Preliminary studies by several groups, including those funded in part by the phase I SBIR award R43-AI40394 to CERES Pharmaceuticals, have demonstrated the potential for FasL-based therapy to prevent transplantation rejection, to treat autoimmune disease, to induce immunological tolerance, and to treat cancer. The "Use of Fas Ligand to Supress T-lymphocyte Mediated Immune Response" is protected by U.S. Patent No. 5,759,536. Donald Bellgrau and Richard C. Duke, inventors. CERES and a large, multinational pharmaceutical company, are the exclusive licensees of this Technology. The overall goal of this phase II application is to develop, and test in pre-clinical trials in mice, commercially useful recombinant mammalian expression plasmid, adenoviral and retroviral gene therapy vectors encoding FasL. These vectors, and strategies for their application, will be licensed to existing pharmaceutical and biotechnology companies for use in filing Investigational New Drug IND) applications with the FDA in anticipation of initiation of phase I clinical trials in humans. Specifically, they will: 1) Generate recombinant mammalian expression plasmid, adenoviral and retroviral vectors encoding mutant forms of mouse and human FasL; 2) Test each of the vectors that have been made, or will be generated, in pre-clinical transplant trials in mice; and 3) License the vectors they have made. Or will generate, to commercial entities with the capability of carrying out human clinical trials. PROPOSED COMMERCIAL APPLICATION: There are innumerable commercial indications for a safe and effective immunosuppressive and/or anti-inflammatory agent for transplantation, autoimmune and other inflammatory disease indications. The currently used drugs, cyclosporin A and corticosteroid analogs, enjoy widespread use but have numerous side effects associated with both short and long-term administration.